During the past year, we discovered that adult filariae differ qualitatively from both their mammalian and arthropod hosts in their ability to oxidize 5-methyltetrahydrofolate (methylFH4) to 5,10-methyleneFH and thence to other FH4 cofactors. The initial oxidation of methylFH4 is catalyzed by methylene FH4 reductase operating in the reverse direction, and we plan to search for selective inhibitors of this filarial enzyme and its associated redox system which remains to be positively identified. Any such selective inhibitor would then be tested against adult Brugia pahangi in vitro and in vivo. We also discovered that adult filariae possess both de novo and salvage enzymatic pathways leading to the synthesis of purine nucleotides. We shall investigate the factors regulating the coordinated activity of these two pathways of purine metabolism, paying particular attention to the kinetic properties of the enzymes involved and their relative affinities for their respective substrates and cofactors.